Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test. |
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Authors: | Jessica Lasky-Su Tobias Banaschewski Jan Buitelaar Barbara Franke Keeley Brookes Edmund Sonuga-Barke Richard Ebstein Jacques Eisenberg Michael Gill Iris Manor Ana Miranda Fernando Mulas Robert D Oades Herbert Roeyers Aribert Rothenberger Joseph Sergeant Hans-Christoph Steinhausen Eric Taylor Kaixin Zhou Margaret Thompson Philip Asherson Stephen V Faraone |
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Institution: | Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York 13210, USA. |
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Abstract: | BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association. |
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Keywords: | ADHD DRD4 family-based association hyperactive-impulsive symptoms inattentive symptoms PBAT |
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